Targeted, Activity-Dependent Spinal Stimulation Produces Long-Lasting Motor Recovery in Chronic Cervical Spinal Cord Injury.

S o far, despite the volumes of research in the field of spinal cord injury (SCI), we are not able to createmeaningful regeneration of the spinal cord. Currently, the best rehabilitative strategies rely on efforts to activate whatever persistently functional circuitry is present. Such a strategy, known as use-dependent movement therapy, works to drive neural plasticity through the repetitive activities in persistent but damaged circuitry. Spinal cord stimulation has been an area of investigation in the field of SCI and has already shown some promise. It is believed that electric stimulation improves excitability and activation of spared pathways and can induce plasticity, thus improving functional motor recovery after SCI. Extrinsic stimulation likely strengthens synaptic connections and reinforces specific circuitry. McPherson et al have recently described a new strategy of activitydependent stimulation using a neuroprosthesis, or neural-computer interface, in a rat model of SCI to improve neural plasticity and to enhance long-lasting durable motor recovery after chronic SCI. Specifically, they hypothesized that timing spinal cord stimulation to the periods of attempted motor function during use-dependent movement therapy could improve further motor recovery in a long-lasting fashion. The neuroprosthesis for this experimentation incorporated electromyography (EMG) for the detection of attempted motor function connected to a device called the Neurochip. The Neurochip is a miniaturized, closed-loops system that can discriminate biophysical signals and deliver contingent electric stimulation, all while operating during normal free behavior. Put simply, with attempted movement of a paretic limb, the EMG detects even minimal motor recruitment and provides information to the Neurochip. The Neurochip can then respond, however programmed, to time electric stimulation to correspond to attempted motor function. The authors designed a protocol using this target activitydependent spinal stimulation (TADSS) during SCI rehabilitation to measure the effectiveness of electric stimulation therapy to restore motor function. A forelimb reach-grab task was used to measure the motor activity of the affected ipsilateral forelimb of 24 female rats before and after a chronic unilateral C4-5 cord contusion. The rats were divided into3 interventional groups: TADSS with physical retraining (n 1⁄4 9), targeted openloop spinal stimulation (TOLSS) with retraining (n 1⁄4 6), and retraining alone (n 1⁄4 9). Directly following the stereotyped cervical SCI, all rats were unable to perform the reachgrab task to any degree. No treatment intervention was administered in the first 6 weeks after SCI. Throughout the first 3 weeks of treatment, all groups showed the same rate and extent of motor recovery (Figure). At week 4, the TADSS treatment group showed a drastic improvement in performance when compared with the 2 other treatment groups. By the end of the 13-week rehabilitation period, the TADSS group showed a 63% recovery of original motor function, whereas the TOLSS and retraining groups showed a 30% and 31% recovery, respectively. Comparison of the TADSS and TOLSS groups indicates that time dependence of the stimulus is a crucial factor in the effectiveness of this method. Stimulation, but not retraining, was then stopped, and further data were collected for 4 weeks to determine the durability of motor function improvement from electric stimulation and retraining. All 3 treatment groups retained the performance success rate demonstrated at the time of rehabilitation cessation, suggesting that the effect is not contingent on long-term delivery of electric stimulation but rather plasticity. Theauthors’ findings suggest that the intrinsic capacity of the nervous system for reorganization can be enhanced by a strategy of coordinated stimulation timed to match a patient’s rehabilitative efforts. Imagine a situation in which we as neurosurgeons are not simply decompressing a damaged cord and stabilizing an unstable injury. A neuroprosthesis could be implanted Figure. Implementation of target activity-dependent spinal stimulation (TADSS). A, a C4-5 hemicontusion damages the corticospinal tracts, resulting in persistent motor deficits in the ipsilesional forelimb. Intraspinal microwires are implanted into ipsilesional elbow and wrist extensor motor regions spanning C6-8 spinal segments and deliver either TADSS or targeted open-loop spinal stimulation. B, the Neurochip continuously records ipsilesional forelimb extensor electromyography (EMG), discriminates salient increases in activity, and delivers ISMS to functionally related spinal motor regions. From McPherson JG, Miller RR, Perlmutter SI. Targeted, activity-dependent spinal stimulation produces long-lasting motor recovery in chronic cervical spinal cord injury. Proc Natl Acad Sci U S A. 2015;112(39):12193-12198. SCIENCE TIMES